T cell responses are critical for providing early control and clearance of many viral infections, but there remain many unknowns concerning T cell immunity in COVID-19. Some T cell responses may even have a detrimental impact on the clinical outcome and contribute to long COVID, a phenomenon that affects roughly 10% of COVID-19 patients, causing them to experience an array of symptoms for a month or longer. In this Perspective, Annika Karlsson and colleagues discuss unresolved questions surrounding T cell immunity against SARS-CoV-2 infection, including one that's important to consider for development of T cell-targeted vaccines: are T cells critical to generate durable immunity to the virus? Other unknown areas include the roles and longevity of SARS-CoV-2-specific memory T cells; the location and function of tissue resident memory T cells; and whether preexisting immunity to SARS-CoV-2 via cross-reactive T cells helps protect against the virus or, rather, exacerbates harmful inflammation. As well, scientists have yet to determine how T cell responses differ depending on disease severity (mild or asymptomatic versus severe or long COVID), and whether genetic factors, such as a patient's HLA type, could influence disease severity. Filling these gaps in knowledge using both animal models and longitudinal studies in large patient cohorts is vital for the formulation of effective COVID-19 vaccines and treatments, the authors say.
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Science Immunology